Karen E Hansen1, Jeri W Nieves2, Sai Nudurupati3, David C Metz4, Maria Claudia Perez3. 1. School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin. Electronic address: keh@medicine.wisc.edu. 2. Mailman School of Public Health, Columbia University, New York, New York. 3. Takeda Development Center Americas, Inc., Deerfield, Illinois. 4. Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Abstract
BACKGROUND & AIMS: Epidemiological studies have associated proton pump inhibitor (PPI) therapy with osteoporotic fractures, but it is not clear if PPIs directly cause osteoporosis. We evaluated the effect of dexlansoprazole and esomeprazole on bone turnover, bone mineral density (BMD), true fractional calcium absorption (TFCA), serum and urine levels of minerals, and levels of parathyroid hormone (PTH) in healthy postmenopausal women. METHODS: We performed a prospective, multicenter, double-blind study of 115 healthy, postmenopausal women (45 to 75 years of age) from November 4, 2010, through August 7, 2014. Women were randomly assigned to groups given dexlansoprazole (60 mg), esomeprazole (40 mg), or placebo daily for 26 weeks. We measured plasma levels of procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide of type 1 collagen (CTX) at 0 (baseline), 13, and 26 weeks. Primary outcomes were percent change in P1NP and CTX between weeks 0 and 26. We also measured changes in serum and urine levels of mineral, BMD, PTH (all subjects), and TFCA (n = 30). RESULTS: Between baseline and week 26, there were no significant within-group differences in markers of bone turnover; there was a nonsignificant increase in CTX levels in the dexlansoprazole group (0.12 ng/mL). The esomeprazole and dexlansoprazole groups had significantly increased levels of P1NP (18.2% and 19.2%, respectively) and CTX (22.0% and 27.4%, respectively) at week 26 compared with the placebo group, although these values remained within normal ranges. There were no statistically significant differences between groups in serum or urine levels of minerals, BMD, or PTH at week 26. PPI therapy did not reduce TFCA. CONCLUSIONS: In a prospective study of postmenopausal women, we found significant increases in markers of bone turnover in women given PPI therapy compared with women given placebo, but levels remained within the normal reference range. We found no significant differences among groups in changes in BMD, PTH, serum or urine levels of minerals, or TFCA. Our findings indicate that 26 weeks of treatment with a PPI has no clinically meaningful effects on bone homeostasis. Clinicaltrials.gov no: NCT01216293.
RCT Entities:
BACKGROUND & AIMS: Epidemiological studies have associated proton pump inhibitor (PPI) therapy with osteoporotic fractures, but it is not clear if PPIs directly cause osteoporosis. We evaluated the effect of dexlansoprazole and esomeprazole on bone turnover, bone mineral density (BMD), true fractional calcium absorption (TFCA), serum and urine levels of minerals, and levels of parathyroid hormone (PTH) in healthy postmenopausal women. METHODS: We performed a prospective, multicenter, double-blind study of 115 healthy, postmenopausal women (45 to 75 years of age) from November 4, 2010, through August 7, 2014. Women were randomly assigned to groups given dexlansoprazole (60 mg), esomeprazole (40 mg), or placebo daily for 26 weeks. We measured plasma levels of procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide of type 1 collagen (CTX) at 0 (baseline), 13, and 26 weeks. Primary outcomes were percent change in P1NP and CTX between weeks 0 and 26. We also measured changes in serum and urine levels of mineral, BMD, PTH (all subjects), and TFCA (n = 30). RESULTS: Between baseline and week 26, there were no significant within-group differences in markers of bone turnover; there was a nonsignificant increase in CTX levels in the dexlansoprazole group (0.12 ng/mL). The esomeprazole and dexlansoprazole groups had significantly increased levels of P1NP (18.2% and 19.2%, respectively) and CTX (22.0% and 27.4%, respectively) at week 26 compared with the placebo group, although these values remained within normal ranges. There were no statistically significant differences between groups in serum or urine levels of minerals, BMD, or PTH at week 26. PPI therapy did not reduce TFCA. CONCLUSIONS: In a prospective study of postmenopausal women, we found significant increases in markers of bone turnover in women given PPI therapy compared with women given placebo, but levels remained within the normal reference range. We found no significant differences among groups in changes in BMD, PTH, serum or urine levels of minerals, or TFCA. Our findings indicate that 26 weeks of treatment with a PPI has no clinically meaningful effects on bone homeostasis. Clinicaltrials.gov no: NCT01216293.